Cardiovascular disease and cerebrovascular disease are the leading causes of morbidity and mortality among persons age 65 and older in the United States, and recognition is increasing for the role of vascular contributions to dementia. Despite the dramatic public health impact of these illnesses, success in identifying the etiology of vascular disease and preventing adverse vascular outcomes has met incomplete success. Endothelial dysfunction (ED) shares many risk factors with cardiovascular and cerebrovascular diseases and vascular dementia, and ED may represent a common pathway leading to these disabling diseases. Unfortunately, little data exists documenting the magnitude of ED or its sequelae in populationbased studies. This investigation will take advantage of an existing, fully funded, community-based longitudinal cohort study of successful aging (Mayo Interdisciplinary Program Project Research Grant for Translational Research - INTRPRT) and a multidisciplinary collaborative effort of the Mayo Clinic Alzheimer's Disease Research Center (ADRC) and Center for Coronary Imaging and Physiology to explore the prevalence and cognitive sequelae of ED in elderly residents of Olmsted County, Minnesota. The broad goals are to identify novel opportunities for prevention and treatment of vascular disease and vascular contributions to dementia. Utilizing the 600 person, community-based ADRC INTRPRT cohort, we will determine the feasibility of non-invasive serial measurements of ED and calculate prevalence of ED in this cohort. Participants will undergo extensive cognitive assessment, and Cox proportional hazards regression will be employed to examine the longitudinal association of ED with cognitive impairment. Adjustment for pre-existing medical, demographic and behavioral characteristics obtained for each participant through the Rochester Epidemiology Project records-linkage system will be made in multivariable models. We expect increasing prevalence of ED with age and an increased risk of cognitive impairment among persons with ED. Documenting our results will advance the understanding of both ED and the etiology of cognitive impairment, identify potential targets for intervention on cognitive decline/dementia, provide preliminary data for future studies of sequelae of ED, and produce information potentially transferable to the study of cardiovascular, cerebrovascular and other vascular diseases.